Project Summary Kidney diseases in general and acute kidney injury (AKI) in particular impose substantial morbidity and mortality; these remain unabated in recent decades despite concerted efforts to reduce both. The overall mission of the University of Alabama at Birmingham (UAB)-University of California San Diego (UCSD) O'Brien Center for AKI Research is to improve the health of patients by fostering research specifically targeted to the prevention and treatment of AKI and its complications. To achieve this mission, this Center crosses institutional boundaries and research fields to harness the momentum and ingenuity of ongoing pre-clinical and clinical research in both institutions. The following aims are proposed: i) facilitate hypothesis-driven research through shared core facilities and leverage these technologies into new projects and collaborations, (ii) foster relevant interactions among UAB-UCSD investigators from different disciplines and extend these interactions to investigators from multiple institutions, (iii) provide, through the Biomedical Research Cores, a Pilot and Feasibility Grants (PAF) Program, and attract new and established investigators to AKI research by capitalizing on our research cores and infrastructure, (iv) build upon the progress during the last cycle by responding to the evolving needs of our investigators, (v) administer an Enrichment Program that delivers outstanding training and education across the continuum of research activity, and (vi) leverage substantial institutional commitments (>$1.5 million) to advance these aims. Three complementary Cores will continue to integrate existing intellectual and technological resources of UAB and UCSD and provide a defined set of services to facilitate investigator-initiated AKI- related research. The Cores include: 1) Resource for Clinical Studies of AKI (clinical research, registry and biorepository including human kidney tissues); 2) Resource for Pre-Clinical Studies of AKI (animal models, small animal imaging and physiology); 3) Bioanalytical Core (bioenergetics, biomarkers, small molecule analysis). A Biostatistical Resource will provide support for the cores and pilot projects. The Center also includes an active and productive PAF program designed to attract new investigators into the field and yield a high return on investment in terms of extramural funding and publications. In the prior 4 years of funding, the Center has galvanized our research community and created a robust collaborative environment particularly for AKI research integrating two institutions and resulting in 220 publications. The Internal Research Base includes 100 investigators (from UAB and UCSD) with NIDDK funding of $9.6 million in annual direct costs and 88 investigators from other institutions that form an Extended Research Base. Twelve pilot awardees were funded, and we propose to fund 3-4 pilots/year in this renewal cycle. The Center will continue to promote a seamless integration of expertise and resources at both institutions for innovative and productive research needed for the translation of new insights into novel therapies for patients with AKI.